• Mieke Boon, Stijn E Verleden, Barbara Bosch, Elise J Lammertyn, John E McDonough, Cindy Mai, Johny Verschakelen, Mariette Kemner-van de Corput, Harm A W Tiddens, Marijke Proesmans, François L Vermeulen, Erik K Verbeken, Joel Cooper, Dirk E Van Raemdonck, Marc Decramer, Geert M Verleden, James C Hogg, Lieven J Dupont, Bart M Vanaudenaerde, and Kris De Boeck.
• 1 Pediatric Pulmonology and Cystic Fibrosis Unit, Department of Pediatrics.
• Am. J. Respir. Crit. Care Med. 2016 Mar 1; 193 (5): 516-26.

RationaleAfter repeated cycles of lung infection and inflammation, patients with cystic fibrosis (CF) evolve to respiratory insufficiency. Although histology and imaging have provided descriptive information, a thorough morphometric analysis of end-stage CF lung disease is lacking.ObjectivesTo quantify the involvement of small and large airways in end-stage CF.MethodsMultidetector computed tomography (MDCT) and micro-CT were applied to 11 air-inflated CF explanted lungs and 7 control lungs to measure, count, and describe the airway and parenchymal abnormalities in end-stage CF lungs. Selected abnormalities were further investigated with thin section histology.Measurements And Main ResultsOn MDCT, CF explanted lungs showed an increased median (interquartile range) number (631 [511-710] vs. 344 [277-349]; P = 0.003) and size of visible airways (cumulative airway diameter 217 cm [209-250] vs. 91 cm [80-105]; P < 0.001) compared with controls. Airway obstruction was seen, starting from generation 6 and increasing to 40 to 50% of airways from generation 9 onward. Micro-CT showed that the total number of terminal bronchioles was decreased (2.9/ml [2.6-4.4] vs. 5.3/ml [4.8-5.7]; P < 0.001); 49% were obstructed, and the cross-sectional area of the open terminal bronchioles was reduced (0.093 mm(2) [0.084-0.123] vs. 0.179 mm(2) [0.140-0.196]; P < 0.001). On micro-CT, 41% of the obstructed airways reopened more distally. This remodeling was confirmed on histological analysis. Parenchymal changes were also seen, mostly in a patchy and peribronchiolar distribution.ConclusionsExtensive changes of dilatation and obstruction in nearly all airway generations were observed in end-stage CF lung disease.

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